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Biomedical subjects

R J Bell

Publications and source records attributed to R J Bell.

At least 37 records · Page 2Linked to original sources

Relaxin in paired samples of serum and milk from women after term and preterm delivery.

In a study to determine if relaxin could be measured in milk and if so to correlate concentrations in milk and serum, paired samples of milk and serum were collected from 12 women 3 days after term delivery (term group), from 16 women 3 days after preterm delivery (preterm group), and from some of these patients 6 weeks after delivery (eight term and six preterm). Relaxin was measured by specific human relaxin radioimmunoassay. Relaxin from milk and sera behaved similarly in the relaxin radioimmunoassay and reverse-phase high-performance liquid chromatography. Concentrations of relaxin in sera and milk collected 3 days after delivery did not differ significantly within the term or preterm groups. Neither were there differences in relaxin levels in sera and milk between the term and preterm groups. At 6 weeks postpartum, relaxin was not measured in any sera but was measured in milk from six of eight patients in the term group and five of six patients in the preterm group. Relaxin concentrations in milk were higher in the preterm group. The presence of relaxin in milk at 6 weeks postpartum suggests a nonluteal site of synthesis.

Chromatography, High Pressure Liquid↗

Relaxin levels in antenatal patients following in vitro fertilization.

The aim of this study was to investigate the relationship between serum relaxin and pregnancy outcome in a group of patients pregnant after in vitro fertilization (IVF). Patients who delivered a single live infant at term after IVF had mean serum levels of relaxin more than double the mean levels in normal antenatal patients. The high relaxin levels were compatible with delivery at term. However, because of the proposed role of relaxin in the process of cervical ripening, the high serum levels may help explain the high rate of preterm labor observed among IVF patients.

Abortion, Spontaneous↗

Antenatal serum levels of relaxin in patients having preterm labour.

This study is the first report of antenatal levels of relaxin measured by homologous radioimmunoassay in peripheral serum from patients who subsequently had a preterm delivery. Serial blood samples were collected antenatally from a group of subjects known to be at increased risk of preterm labour because of a past history of shortened pregnancy. Serum relaxin was measured using an homologous radioimmunoassay based on a synthetic bioactive analogue of the native hormone. In women whose pregnancies ended preterm most measurements were within the range of values previously established in normal antenatal patients although some measurements early in pregnancy were above the normal range. These findings suggest that low serum levels of relaxin are not causatively related to the onset of labour before term.

Female↗

Relaxin in human pregnancy serum measured with an homologous radioimmunoassay.

This study reports serum levels of relaxin in normal and special-interest pregnancies using an homologous radioimmunoassay for human relaxin. The mean levels in uncomplicated antenatal patients were lower than those reported in studies using heterologous assays, but the trend in serum levels was similar. Serum levels peaked at ten weeks' gestation and decreased progressively to term. Relaxin was detectable in all pregnant subjects assessed at the time of the first missed menses. The mean relaxin levels in patients having in vitro fertilization and embryo transfer who subsequently delivered a single infant were significantly higher than those in normal antenatal patients at an equivalent gestational age. Patients with twin pregnancies after in vitro fertilization and embryo transfer generally had higher levels than patients with single pregnancies. Some pregnant patients who aborted after in vitro fertilization and embryo transfer had declining levels of relaxin before 40 days postlaparoscopy.

Embryo Transfer↗

Radioimmunoassay of relaxin in pregnancy with an analogue of human relaxin.

A radioimmunoassay for relaxin was developed in which a synthetic analogue of human relaxin was used as standard, tracer, and immunogen. Relaxin could not be measured in sera from men or non-pregnant women, but was measurable in pregnant women from the tenth week of gestation until term. Concentrations ranged from 0.19-1.18 ng/ml, with highest levels measured in the first trimester.

Animals↗

Regulation and function of arginine vasopressin in pregnant sheep.

The aim of this study was to investigate the regulation and function of arginine vasopressin (AVP) in pregnant sheep. The mean plasma osmolality of nonpregnant ewes (298 +/- 1.0 mosmol/kg, n = 8) was not significantly different from that of late pregnant ewes (295 +/- 1.1 mosmol/kg, n = 21). The mean resting plasma [AVP] of nonpregnant ewes (4.1 +/- 0.6 pg/ml,n = 8) was not significantly different from that of pregnant ewes (3.3 +/- 0.3 pg/ml,n = 21). In a series of dehydration experiments it was established that the slope of the function relating log [AVP] to plasma osmolality for pregnant ewes (n = 13) was not significantly different from the slope of the function relating log [AVP] to plasma osmolality for nonpregnant ewes (n = 4). When AVP was infused into water-loaded ewes, a significant decrease in urinary flow rate and free water clearance occurred at an infusion rate of 0.003 microgram/h in both the pregnant (n = 4) and nonpregnant (n = 4) animals. Both groups achieved negative free water clearance at an infusion rate of 0.01 microgram/h. These findings suggest that pregnancy does not alter the relationship between plasma osmolality and plasma [AVP] or the renal responsiveness to AVP in sheep.

Animals↗

Effect of long-term infusion of ovine corticotrophin-releasing factor in the immature ovine fetus.

Synthetic ovine corticotrophin-releasing factor (oCRF) was infused continuously into the jugular veins of six ovine fetuses for 5-11 days. Two fetuses receiving 0.1 and 1.0 microgram oCRF/h from gestational days 134 and 135 respectively, lambed prematurely on days 141 and 140 respectively. Three out of four fetuses receiving oCRF at 2.4 micrograms/h, from 125 days of gestation, delivered spontaneously at 131, 131 and 136 days, whilst one died in utero at 132 days. Two fetuses receiving vehicle only or oCRF intra-amniotically, were born at 148 and 145 days respectively, whilst six fetuses chronically cannulated but not infused were born at 149.8 +/- 2.1 (S.D.) days. In ewes lambing at term, maternal plasma progesterone concentrations were 41.4 +/- 11.4 (S.E.M.; n = 5), 28.8 +/- 7.8 (n = 6), 17.1 +/- 4.8 (n = 5) and 7.9 +/- 1.1 (n = 4) nmol/l on 3, 2, 1 and 0 days respectively before the lambs were born. No such decrease in maternal plasma progesterone concentrations was seen in the oCRF-infused fetuses. Fetal plasma concentrations of immunoreactive ACTH were maintained above normal in oCRF-infused fetuses, but some desensitization to bolus oCRF injections occurred in these fetuses. Four of the five fetuses born prematurely were sufficiently mature to survive, being able to stand, breathe and suckle. It is concluded that continuous oCRF infusions into immature fetuses can accelerate maturation of a number of organs and systems culminating in the premature delivery of viable lambs.

Adrenocorticotropic Hormone↗

The effect of maternal water deprivation on ovine fetal blood volume.

Fetal blood volume was measured in pregnant ewes bearing chronically cannulated fetuses in the last third of gestation. The increase in fetal blood volume secondary to growth was established from serial measurements in four control animals. The effect of maternal dehydration was assessed by measuring the change in fetal blood volume during twelve episodes of maternal water deprivation in another six ewes. Fetal blood volume increased during each episode of maternal dehydration. In five experiments the rate of increase was greater than controls and in seven experiments the rate of increase was less than controls. Thus, fetal hypovolaemia does not occur during maternal dehydration in the ovine fetus in the last third of gestation.

Animals↗

A child with a recombinant of chromosome 8 inherited from her carrier mother.

A female child with mental retardation and dysmorphic features was found to have a duplication deficiency of chromosome 8: rec(8)dup q,inv(8)(p23q24), a recombinant product derived from a familial pericentric inversion, inv(8)(p23q24)mat. Clinical features of this previously undescribed inversion product are compared with other reported cases of partial trisomy for the distal long arm of chromosome 8, since this segment is thought to be primarily responsible for the phenotypic features of the trisomy 8 syndrome.

Adult↗

The role of fetal adrenal hormones in the switch from fetal to adult globin synthesis in the sheep.

The switch from gamma (fetal) to beta (adult) globin production was studied by the analysis of globin synthesis in chronically cannulated ovine fetuses and newborn lambs. The gamma/alpha globin synthesis ratio decreased from 0.98 +/- 0.11 (S.D.) (n = 4 samples) at 100-120 days of gestation to 0.15 +/- 0.07 (n = 4) in lambs of 150-156 days post-conception, and the beta/alpha synthesis ratio increased from 0.04 +/- 0.06 (n = 4) to 1.13 +/- 0.21 (n = 4) over the same period. In bilaterally adrenalectomized fetuses, which survived in utero until 151-156 days, the gamma/alpha and beta/alpha synthesis ratios were 0.64 +/- 0.14 (n = 3) and 0.25 +/- 0.07 (n = 3) respectively in the 150- to 156-day period. Bilateral adrenalectomy did not affect the time of onset of beta globin synthesis, but significantly decreased the rate. In one bilaterally adrenalectomized fetus the infusion of increasing concentrations of cortisol restored the rate of beta globin synthesis to normal. Treatment of three intact fetuses with 100 micrograms cortisol/h for 3 weeks, from 100 to 121 days, did not affect the timing or rate of switch from gamma to beta globin synthesis. Thus fetal adrenal secretions, probably cortisol, affected the rate of change of gamma to beta globin synthesis but other factors must have been involved in the initiation of the switch.

Adrenal Cortex Hormones↗

Effects of maternal sodium depletion on the composition of ovine fetal fluids.

Effects of maternal sodium depletion on the composition of ovine fetal fluids were studied. Maternal Na depletion was achieved by 48-h drainage of parotid saliva. There was a significant decrease in both maternal and fetal plasma Na concentration, indicating that both mother and fetus had experienced the Na-depletion stimulus. There was a significant increase in maternal blood aldosterone but the change in fetal blood aldosterone was not significant. In animals where there was an increase in fetal blood aldosterone the increase could be accounted for by transfer of aldosterone across the placenta from the mother. There was a significant decrease in fetal urinary Na concentration and Na excretion and the urinary Na/K ratio fell in seven out of eight studies. These observations are consistent with the hypothesis that fetal Na depletion sensitizes the fetal kidney to the action of circulating aldosterone as in the adult.

Aldosterone↗

Development of the hypothalamic-pituitary-axis in the ovine fetus: ontogeny of action of ovine corticotropin-releasing factor.

In samples from twenty chronically cannulated ovine fetuses the plasma immunoreactive adrenocorticotrophin (ACTH) concentrations were 12.5 +/- 3.2(8), 15.2 +/- 4.1(9) and 21.2 +/- 5.6(8) pg/ml at periods, prior to parturition, of -30 to -35, -25 to -29 and -20 to -24 days respectively. Values are mean +/- SEM (number of samples). These values were not significantly different from each other but were significantly lower (P less than 0.02) than values in the next two age groups -36.0 +/- 4.9(7) pg/ml at -19 to -15 days, and 39.6 +/- 6.6(11) pg/ml at -14 to -9 days. A further significant increase (P less than 0.05) occurred in the -8 to -3 day period, ACTH being 53.9 +/- 5.4(12) pg/ml. On day of delivery two samples had values of 325 and 360 pg/ml. A single injection, intravenously of 1.0 microgram ovine corticotrophin-releasing factor (O-CRF), caused a significant increase in fetal plasma ACTH concentrations in fetuses of -6 to -23 days prior to delivery but not in fetuses -24 to -35 days prior to parturition. The maximum values of ACTH after O-CRF were significantly greater in fetuses -2 to 0 days prior to parturition than in younger fetuses (P less than 0.01). In 6 experiments in 4 fetuses (parturition -1 to -13 days) the effect of 1.0 microgram O-CRF persisted for at least 2.5 h. The results support the hypothesis that the pituitary release of ACTH changes sensitivity to hypothalamic O-CRF at least twice during the last fifth of gestation; an increasing sensitivity is seen as term approaches.

Adrenocorticotropic Hormone↗

The value of urine osmolality as an index of stress in the ovine fetus.

In ovine fetuses, during 100-130 days of gestation, urine osmolalities less than 175 mosmol/kg water were associated with plasma immunoreactive adrenocorticotrophin (ACTH) concentrations below 40 pg/ml in 40/41 samples. In 18/29 fetuses with urine osmolalities greater than 175 mosmol/kg water plasma ACTH was significantly elevated. In 38 samples of fetal blood there was a significant correlation between plasma ADH and ACTH concentrations. By least squares regression the equation to the line was [ACTH] = 5.06 + 3.70 [ADH] (r = 0.62, P less than 0.001). In 50 samples from fetuses of gestational ages 100-140 days, with urine osmolalities of 302 +/- 86 mosmol/kg (mean +/- SD) the blood pH, pO2 and pCO2 values were not significantly different from those in 50 samples from fetuses with urine osmolalities of 125 +/- 22 mosmol/kg. It is proposed that the measurement of fetal urine osmolality provides a good index of fetal stress. A fetus with a urine osmolality less than 175 mosmol/kg is almost invariably in the optimum, unstressed condition.

Adrenocorticotropic Hormone↗

Gestation-dependent aspects of the response of the ovine fetus to the osmotic stress induced by maternal water deprivation.

Water deprivation was produced in pregnant sheep by withholding water for 24 h and then giving them 500 ml/d for the subsequent 3 d. All ewes bore chronically cannulated fetuses. Eleven experiments were performed in group I animals (gestation periods of 107-119 d at maximal stress) and eight experiments in group II (126-144 d of gestation). Measurements were made of maternal and fetal plasma osmolalities, fetal urine flow rate and osmolality, amniotic fluid osmolality and fetal plasma antidiuretic hormone (ADH) concentration. The experimental protocol produced a larger increment in maternal and fetal plasma osmolalities in group I than in group II (P less than 0.025). For group I fetuses the relationship between plasma ADH concentration, [ADH] and plasma osmolality was log [ADH] = -4.50 + 0.0174 (osmol) which was significantly different from that for group II fetuses, log [ADH] = -10.46 + 0.0373 (osmol) (P less than 0.02). Thus plasma [ADH] was significantly greater, at a given plasma osmolality, in older (group II) than younger (group I) fetuses. For a given value of fetal plasma [ADH] there was a greater reduction in fetal urine free water clearance in older than younger fetuses. Water deprivation of the ewe did disturb the composition of amniotic fluid and the trend in amniotic fluid osmolality followed the trend in fetal urinary osmolality.

Amniotic Fluid↗

Synthetic ovine corticotropin-releasing factor stimulates adrenocorticotropin release in the ovine fetus over the last fifth of gestation.

Synthetic ovine corticotropin-releasing factor (0.1-1.0 micrograms) was injected intravenously to 6 chronically cannulated ovine fetuses between 104 and 149 days of gestation (term 142-152 days). Arterial plasma immunoreactive adrenocorticotropin was first elevated by this procedure if the fetuses were between 118 and 130 days of gestation, and an increased response occurred later in gestation. This suggests that a progressive reset of the hypothalamic-pituitary-adrenal feedback relationship occurs over the last 2-3 weeks of gestation in the ovine fetus.

Adrenocorticotropic Hormone↗